MCSD Proposal: Towards the physiologic function of MiRP-3. The research: Potassium channels catalyze the movement of K+ ions across the cell membrane, and their function is essential for cellular electrical activity and electrolyte homeostasis. Many K+ channels are regulated by accessory-subunit proteins, which can be required for normal physiologic function and allow for the channels to adapt to changes of environmental conditions. This application describes the study of the beta subunit MiRP-3, a novel member of the MinK-related peptide superfamily, which can modulate the properties of such K+ channels. We present preliminary evidence that suggests a role for MiRP-3 in modulating vascular smooth-muscle function as well as renal potassium secretion and acid-base homeostasis. We propose a plan to study MiRP-3 and a physiologically relevant partner. MiRP-3 will be evaluated for its effects on K+ channels and how such modulation can influence physiologic processes. The candidate: Dr. Daniel I. Levy trained as an ion-channel physiologist (Univ. Penn. Sch. Med.), which motivated his decision to choose a residency in Internal Medicine (Hosp. Univ. Pennsylvania) and subspecialty training in Nephrology (Yale). He is now an Instructor in the Nephrology section at the University of Chicago. His career goal is to run a basic research laboratory investigating the mechanistic principles of ion channel function and their implications for human diseases. This proposal is submitted to support his career development in the disciplines of biophysics, biochemistry, and molecular genetics, to enable him to become an independent investigator and academically viable clinician-scientist. The environment: The primary sponsor, Dr. Steve Goldstein, is a leading investigator in potassium channel research and ion channelopathies. The first three MinK-related peptides were identified and expressed in his laboratory, which is rich in biophysical, molecular biology, and molecular genetics expertise. The Department of Medicine and the Department of Neurobiology, Pharmacology & Physiology at the University of Chicago include an internationally recognized cadre of ion channel researchers.